Chitosan nanoparticles as delivery systems for doxorubicin

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Abstract

The aim of this paper was to evaluate the potential of chitosan nanoparticles as carriers for the anthracycline drug, doxorubicin (DOX). The challenge was to entrap a cationic, hydrophilic molecule into nanoparticles formed by ionic gelation of the positively charged polysaccharide chitosan. To achieve this objective, we attempted to mask the positive charge of DOX by complexing it with the polyanion, dextran sulfate. This modification doubled DOX encapsulation efficiency relative to controls and enabled real loadings up to 4.0 wt.% DOX. Separately, we investigated the possibility of forming a complex between chitosan and DOX prior to the formation of the particles. Despite the low complexation efficiency, no dissociation of the complex was observed upon formation of the nanoparticles. Fluorimetric analysis of the drug released in vitro showed an initial release phase, the intensity of which was dependent on the association mode, followed by a very slow release. The evaluation of the activity of DOX-loaded nanoparticles in cell cultures indicated that those containing dextran sulfate were able to maintain cytostatic activity relative to free DOX, while DOX complexed to chitosan before nanoparticle formation showed slightly decreased activity. Additionally, confocal studies showed that DOX was not released in the cell culture medium but entered the cells while remaining associated to the nanoparticles. In conclusion, these preliminary studies showed the feasibility of chitosan nanoparticles to entrap the basic drug DOX and to deliver it into the cells in its active form.

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Most cited references 17

Record: found
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Article: not found

Expression of Multidrug Resistance Gene in Human Cancers

M Lieber, J Cossman, M M Gottesman … (1989)

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Article: not found

Deciphering the fluorescence signature of daunomycin and doxorubicin.

Kerry K Karukstis, Elizabeth H.Z. Thompson, Jennifer A Whiles … (1998)

The fluorescence characteristics of daunomycin (DNM), doxorubicin (DXR), and other anthracycline drugs are often used to monitor localization of the drug within lipid bilayers and liposomal delivery systems and to assess interaction of the drug with DNA and other macromolecules. However, the binding of DNM and DXR to proteins and membrane systems has been observed to exhibit variable effects on the anthracycline's fluorescence. We have delineated the spectroscopic response of DXR and DNM to their surroundings in several systems, including solvents of differing dielectric constant, aqueous solutions of varying pH or fluorophore concentration, and the reverse micellar system of AOT/heptane/water with a range of doxorubicin concentrations. We have observed that the ratio of fluorescence intestinal at the two principal lambda max values shows a parabolic dependence on solvent dielectric constant, i.e. inverted solvatochromism. This behavior has been overlooked by previous investigators and, together with the appearance of a long-wavelength band near 630 nm in solvents of low dielectric strength (also previously not reported), is key to understanding the partitioning of anthracyclines in membrane systems as well as resolving the conflicting interpretation of data in the literature.

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Doxorubicin-loaded nanospheres bypass tumor cell multidrug resistance.

C Cuvier, L Roblot-Treupel, J.M. Millot … (1992)

We have demonstrated that in vitro resistance of tumor cells to doxorubicin (Dox) can be fully circumvented by using doxorubicin-loaded nanospheres (Dox-NS), consisting of biodegradable polyisohexylcyanoacrylate polymers of 300 nm diameter and containing 2.83 mg of Dox per 31.5 mg of polymer. Five different multidrug-resistant cell lines, characterized by mdr1 amplification, were used in this study: Dox-R-MCF7, a human breast adenocarcinoma; SKVBL1, a human ovarian adenocarcinoma; K562-R, a human erythroleukemia; and two murine lines: P388-Adr-R, a monocytic leukemia of DBA2 mouse, and LR73MDR, a Chinese hamster ovarian cell line. These lines were 38.7, 210, 232, 143 and 20 times more resistant than their corresponding sensitive counterparts, respectively. Using Dox-NS, we obtained complete reversion of drug resistance in vitro, i.e. cell growth inhibition comparable with that obtained with sensitive cells exposed to free Dox. In vivo, we significantly prolonged the survival of DBA2 mice which had previously received P388-Adr-R cells by i.p. injections of Dox-NS, while free Dox injection was ineffective toward this rapidly growing tumor. (Prolongation of survival time: 115% vs 167% after Dox vs Dox-NS treatment, respectively.) Using the MCF7 cell line and its resistant variant, we studied the intracellular concentration and the cytoplasmic and nuclear distribution of Dox by laser microspectrofluorometry (LMSF). In sensitive cells, we observed a similar accumulation and distribution of Dox whatever the form of Dox delivery, i.e. whether free or carried by nanospheres. Analysis by LMSF showed that 99% of intranuclear Dox was bound to DNA after treatment with both forms of Dox. Of Dox, 81 and 83% were found in the intranuclear compartment of sensitive cells incubated with free Dox and Dox-NS, respectively. Resistant cells incubated with Dox-NS accumulated the same amount of Dox as sensitive cells incubated with free Dox or with Dox-NS. Dox, when loaded in nanospheres, bypasses the efflux mechanism responsible for multidrug resistance. LMSF analysis showed that Dox, transported and released by nanospheres, interacts with DNA identically in sensitive and resistant cells.